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Synthesis 2023; 55(21): 3644-3651
DOI: 10.1055/a-2088-4302
special topic
C–H Bond Functionalization of Heterocycles

Selective Deuteration of Heterocycle N-Oxides via Iridium-Catalysed Hydrogen Isotope Exchange

Philippa K. Owens
a   Department of Pure and Applied Chemistry, University of Strathclyde, Thomas Graham Building, 295 Cathedral Street, Glasgow G1 1XL, UK
,
Blair I. P. Smith 
a   Department of Pure and Applied Chemistry, University of Strathclyde, Thomas Graham Building, 295 Cathedral Street, Glasgow G1 1XL, UK
,
Sebastien Campos
b   Medicines Research Centre, GlaxoSmithKline R & D, Stevenage SG1 2NY, UK
,
David M. Lindsay 
a   Department of Pure and Applied Chemistry, University of Strathclyde, Thomas Graham Building, 295 Cathedral Street, Glasgow G1 1XL, UK
,
William J. Kerr  ∗
a   Department of Pure and Applied Chemistry, University of Strathclyde, Thomas Graham Building, 295 Cathedral Street, Glasgow G1 1XL, UK
› Author AffiliationsThe authors thank the University of Strathclyde (B.I.P.S.; studentship), and GlaxoSmithKline and the EPSRC (P.K.O.; studentship EP/L505663/1) for funding.
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Abstract

An iridium(I) N-heterocyclic carbene/phosphine complex has been applied to the C–H activation and hydrogen isotope exchange of quinoline N-oxides. The isotope labelling proceeds under exceptionally low catalyst loadings of 0.25 mol% and delivers products with high levels of deuterium incorporation selectively at the C8 position. A broad substrate scope is demonstrated, with the method tolerant of electron-poor and -rich substrates, and of substitution adjacent to the site of C–H activation. The isotope label is fully retained under standard deoxygenation conditions to give the corresponding labelled quinoline, and the labelling and deoxygenation can be combined in a one-pot procedure.

Key words

iridium - catalysis - C–H activation - isotope labelling - quinolines - N-oxides

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/a-2088-4302.
  • Supporting Information


Publication History

Received: 01 March 2023

Accepted after revision: 08 May 2023

Accepted Manuscript online:
08 May 2023

Article published online:
01 June 2023

© 2023. Thieme. All rights reserved

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